Drug Interaction Report

ADJUST DOSE: Coadministration with potent inducers of CYP450 3A4 may decrease the plasma concentrations of eravacycline, which undergoes oxidation by CYP450 3A4 and flavin monooxygenase (FMO). When eravacycline was given with the potent CYP450 3A4 inducer, rifampin, eravacycline systemic exposure (AUC) decreased by 35% and clearance increased by 54%. Reduced therapeutic efficacy of eravacycline may occur.

MANAGEMENT: Eravacycline dosage should be increased to 1.5 mg/kg every 12 hours when used with potent CYP450 3A4 inducers. When a CYP450 3A4 inducer is started, it is important to remember that they exert their effect in a time-dependent manner and may take at least 2 weeks to reach maximal effect. Likewise, when discontinuing a CYP450 3A4 inducer, the induction may take at least 2 weeks to decline. No dosage adjustment is warranted when eravacycline is used with a weak or moderate inducer.

ADJUST DOSING INTERVAL: Administration with food may increase the oral bioavailability of rifapentine and reduce the incidence of gastrointestinal adverse events. Administration with a high fat meal typically increases rifapentine's maximum concentration (Cmax) and systemic exposure (AUC) by approximately 40% to 50% over that observed when rifapentine is administered under fasting conditions. Rifapentine is often prescribed in combination with isoniazid. When single doses of rifapentine (900 mg) and isoniazid (900 mg) were administered with a low fat, high carbohydrate breakfast, the Cmax and AUC of rifapentine increased by 47% and 51%, respectively. On the other hand, isoniazid's Cmax and AUC decreased by 46% and 23%, respectively.

MANAGEMENT: Products containing oral rifapentine as the sole ingredient recommend administration with a meal to increase bioavailability and reduce the occurrence of gastrointestinal upset, nausea, and/or vomiting. Consultation of product labeling for combination products and/or relevant guidelines may be helpful if rifapentine is combined with a medication that is typically taken on an empty stomach.